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The expression of disease-specific membrane proteins (MPs) is a crucial indicator for evaluating the onset and progression of diseases. Urinalysis of in situ MPs has the potential for point-of-care disease diagnostics, yet remains challenging due to the lack of molecular reporter to transform the expression information of in situ MPs into the measurable urine composition. Herein, a series of tetrahedral DNA frameworks (TDFs) are employed as the cores of programmable atom-like nanoparticles (PANs) to direct the self-assembly of PAN reporters with defined ligand valence and spatial distribution. With the rational spatial organization of ligands, the interaction between PAN reporters and MPs exhibits superior stability on cell-membrane interface under renal tubule-mimic fluid microenvironment, thus enabling high-fidelity conversion of MPs expression level into binding events and reverse assessment of in situ MP levels via measurement of the renal clearance efficiency of PAN reporters. Such PAN reporter-mediated signal transformation mechanism empowers urinalysis of the onset of acute kidney injury at least 6 h earlier than the existing methods with an area under the curve of 100%. This strategy has the potential for urinalysis of a variety of in situ membrane proteins., (© 2023 Wiley-VCH GmbH.)

BACKGROUND Studies have shown that increased platelet aggregation in patients with decompensated cirrhosis indicates higher risk of further decompensation and death, but studies on the association between platelet aggregation function and early postoperative survival in orthotopic liver transplantation (OLT) patients are rare. We conducted a retrospective study to investigate whole-blood platelet aggregation during the perioperative period of OLT patients and its association with clinical outcomes. MATERIAL AND METHODS Adult patients who underwent OLT between January 1 and April 30, 2021 were retrospectively reviewed. Laboratory test results indicating primary hemostasis were analyzed. The generalized linear model was used to investigate the association between primary hemostasis parameters and survival. RESULTS A total of 256 patients were enrolled. The median platelet count (PLT) was 61.5 (39.5-106.3)×109/L before transplantation. The median MA value was 43.1 (34.5-56.2) mm. From the 1st to the 3rd day after transplantation, PLT and MA both indicated a significant decrease. Two weeks after transplantation, PLT rose to 143.0 (85.0-209.0)×10⁹/L, and the MA value rose to 56.7 (52.2-62.7) mm. On multivariate analysis, PLT at 1 week after transplantation (OR: 1.07; P=0.006) and MA value (OR: 1.12; P=0.003) were independently associated with outcome. The AUROC of the model combined with MA value, MELD score, and age was 0.945 (95% CI: 0.911-0.978). CONCLUSIONS The change in primary hemostasis during the early postoperative period of adult OLT is mainly characterized by the increase of platelet count and function 14 days after transplantation. Higher PLT was associated with higher survival at 14 days after transplantation, while a higher PLT ratio was associated with survival at 3 months after transplantation. Based on comprehensive consideration, the model combined with MA value, MELD score, and age more reliably indicated the associated with early survival after transplantation.

Liver cancer is an aggressive tumor originating in the liver with a dismal prognosis. Current evidence suggests that liver cancer is the fifth most prevalent cancer worldwide and the second most deadly type of malignancy. Tumor heterogeneity accounts for the differences in drug responses among patients, emphasizing the importance of precision medicine. Patient-derived models of cancer are widely used preclinical models to study precision medicine since they preserve tumor heterogeneity ex vivo in the study of many cancers. Patient-derived models preserving cell-cell and cell-matrix interactions better recapitulate in vivo conditions, including patient-derived xenografts (PDXs), induced pluripotent stem cells (iPSCs), precision-cut liver slices (PCLSs), patient-derived organoids (PDOs), and patient-derived tumor spheroids (PDTSs). In this review, we provide a comprehensive overview of the different modalities used to establish preclinical models for precision medicine in liver cancer., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Chen, Li, Wang, Yan, Tao, Song, Xi, He and Xia.)

This study investigated the role of N6-methyladenosine RNA methylation in liver regeneration following partial hepatectomy in mice. We created a liver-specific knockout mouse model by the deletion of Mettl3, a key component of the N6-methyladenosine methyltransferase complex, using the albumin-Cre system. Mettl3 liver-specific knockout mice and their wild-type littermates were subjected to 2/3 partial hepatectomy. Transcriptomic changes in liver tissue at 48 h after partial hepatectomy were detected by RNA-seq. Immunohistochemistry and immunofluorescence were used to determine protein expression levels of Ki67, hepatocyte nuclear factor 4 alpha, and cytokeratin 19. Terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling was also performed. Liver weight/body weight ratios after partial hepatectomy were significantly lower in Mettl3 liver-specific knockout mice than in wild-type mice at 48 h after 2/3 partial hepatectomy (3.1% ± 0.11% vs. 2.7% ± 0.03%). Compared with wild-type littermates, Mettl3 liver-specific knockout mice showed reduced bromodeoxyuridine staining and reduced Ki-67 expression at 48 h after 2/3 partial hepatectomy. RNA-seq analysis showed that Mettl3 liver-specific knockout delayed the cell cycle progression in murine liver by downregulating the expression levels of genes encoding cyclins D1, A2, B1, and B2. Loss of Mettl3-mediated N6-methyladenosine function led to attenuated liver regeneration by altering the mRNA decay of suppressor of cytokine signaling 6, thereby inhibiting the phosphorylation of signal transducer and activator of transcription 3 during early liver regeneration. These results demonstrated the importance of N6-methyladenosine mRNA modification in liver regeneration and suggest that Mettl3 targeting might facilitate liver regeneration., (© 2020 Chongqing Medical University. Production and hosting by Elsevier B.V.)

Objective: To investigate the effectiveness of reverse island flaps of digital artery parallel for repairing degloved injuries of the fingertip., Methods: Between June 2008 and January 2010, 13 cases of degloved injuries of the fingertip were treated. There were 8 males and 5 females with an average age of 34 years (range, 19-62 years). The causes of injuries were as follow: impact and press injury in 5 cases, wringer injury in 7 cases, and crush injury in 1 case. The injured fingers were comprised of index finger in 6 cases, middle finger in 4 cases, ring finger in 2 cases, and little finger in 1 case. The size of skin and soft tissue defect ranged from 2.0 cm x 1.8 cm to 3.0 cm x 2.5 cm. Three cases complicated by fracture of the distal phalanx, 1 case by rupture of the insertion of extensor tendon, and 1 case by rupture of the insertion of flexor tendon. The average time from injure to surgery was 4 hours (range, 1 hour and 30 minutes-12 hours). Two neighboring skin flaps located in the same course of digital artery were adopted to repair defect of the fingertip. The size of proximal skin flap ranged from 1.2 cm x 1.0 cm to 2.0 cm x 1.5 cm and the size of distal skin flap ranged from 1.1 cm x 1.0 cm to 1.5 cm x 1.3 cm. The free skin grafts were used to repair the donor sites., Results: Circulation crisis occurred in 1 case at 2 hours after operation and was eliminated by interval disconnecting. The other flaps and skin grafts survived and the wounds healed by first intention. The patients were followed up 6-18 months (mean, 10 months). All flaps presented the satisfactory appearance and texture, and the flexion and extension function of wounded fingers recovered to normal. Two-point discrimination ranged from 7 to 11 mm at last follow-up. According to the functional assessment criteria of upper limb formulated by the Hand Surgery Branch of Chinese Medical Association, the results were excellent in 9 cases, good in 3 cases, and fair in 1 case with an excellent and good rate of 92.3%., Conclusion: Based on the anatomical features of communicating branches of distal interphalangeal joint, two neighboring flaps located in the same course of digital artery are adopted to repair soft tissue defect of the fingertip. This surgical method is a simple and effective method.